DEPENDING on one's perspective, the struggle to gain dominion over malaria can be seen either as a primer of the possible in infectious-disease control or as classic tragedy. All but obliterated in the developed world half a century ago, and suppressed in the Third World in the 1950s and 1960s, malaria has since returned in full force to North Africa, India, Southeast Asia, China, South America, and the Caribbean. Worldwide incidence of the disease has quadrupled in the past five years, and resistance to available drugs for prevention and treatment is growing rapidly. Nearly 40 percent of the world's population lives in regions where malaria is endemic, and millions more live in areas that are encountering the disease for the first time in decades. Europe has had outbreaks, and in the United States 1,000 to 1,200 cases annually have been reported in recent years. But the Centers for Disease Control and Prevention estimates that cases reported in the United States represent only about half the actual incidence. Every year approximately seven million American tourists and business people spend time in regions where malaria is endemic, as do military personnel and foreign visitors to the United States, and it is likely that thousands arrive here with malaria parasites in their bodies. As a consequence, locally transmitted malaria, absent from the United States for roughly thirty years, has returned. Since 1988 locally transmitted malaria has appeared in California, Texas, Michigan, Florida, New Jersey, and New York City. Anopheles mosquitoes -- members of the genus that carries malaria parasites -- are common almost everywhere in the United States and, for that matter, in most populated regions of the world.
Nonetheless, the United States has shown little interest in the problem. Malaria is transferable in blood, yet it is not screened for in the American blood supply. The country's Anopheles mosquito population has gone unmonitored for more than fifty years. "We just don't know the potential for transmission," says John Beier, a professor of tropical medicine at Tulane University. Temperature and humidity may well be among the most important factors in the rate of spread of the disease, yet we have only a vague notion of what effect, if any, climate change will have on malaria transmission -- if, for example, global warming can be expected to bring malaria and other mosquito-borne diseases north from Mexico. Most Americans seem to think the disease has been eradicated or, at worst, is confined to the tropics. In fact there are few places on earth that cannot sustain a malaria epidemic.
Dyann Wirth, a professor of tropical medicine at the Harvard School of Public Health, insists that Americans must stop thinking of malaria as purely a Third World disorder. "The official CDC line is that widespread malaria in the United States is unlikely," she told me recently. "But we could have mini-epidemics, established pockets of disease that would be very expensive to control." Vector-borne diseases -- diseases that are transmitted by way of a third organism, such as the mosquito -- have a much higher reproductive rate than other diseases and pass through a population much more quickly. "Each case of AIDS," Wirth says, "passes along, on average, two to ten additional cases of AIDS. A case of malaria can result in as many as a hundred more cases of malaria. So the multiplier effect is quite substantial." And in this era of tight government budgets there is ample reason to worry that erosion of our public-health infrastructure and the denial of affordable health care to recent immigrants and the poor will encourage the spread of malaria in the United States.
Last year Vice President Albert Gore told an audience at the National Council for International Health that emerging infectious disease was "one of the most significant health and security challenges facing the global community," and announced a policy on infectious-disease control that directed the United States to "work with other nations and international organizations to establish a global infectious-disease surveillance-and-response system." But his statement did not mention funding, and the war on emerging disease it proposes is well beyond the current means of any government research or health agency.
Although the U.S. government is the world's single largest supporter of malaria research, we spend relatively little on the problem -- roughly $40 million annually, most of it administered by the Department of Defense, the U.S. Agency for International Development, and the National Institute of Allergy and Infectious Disease. The Defense Department seeks to protect the U.S. military from acquiring malaria abroad, and focuses on short-term efforts to benefit soldiers. USAID is controversial among scientists, who complain that the agency has spread itself too thin, hiring consultants who, as one infectious-disease expert put it, "know a lot about economics but not a damn thing about disease." Since USAID funding takes into account particular strategic and political interests of the United States, malaria in Africa is for the most part not a priority. And NIAID, an organization with unquestioned scientific expertise, devotes less than one percent of its budget to malaria -- far too little to sustain a strong research base. The CDC also has a role to play. Stephen Morse, a virologist at the Columbia University School of Public Health, says, "The CDC is critical for world control of this disease, yet it's operating on a shoestring." Daniel Colley, who directs the Division of Parasitic Diseases at the CDC, agrees. "Most people assume that we're capable of doing considerably more than we can," he says. "The public-health challenges of malaria are enormous, and we're limited by manpower, time, and financing in our ability to tackle many critical tasks. In relation to the magnitude of the problem, support for research and control of tropical diseases is minimal in this country. Compounding this situation, parasitology has faded from the curriculum of many medical schools in the United States, so although in a global environment the medical community should know about this problem, it largely doesn't."
The international funding picture is equally dismal -- one scientist describes the total infectious-disease budget of the World Health Organization as "at best slightly larger than the budget of a major teaching hospital in Boston." Roughly $85 million a year of public-sector funds is spent internationally on malaria -- only about two cents for every reported case of the disease. As one adage has it, "Money is not a problem in malaria research, because, basically, there is no money." Stephen Morse warns that the lack of international attention to the disease amounts to sheer recklessness. "We have been trafficking in microbes -- albeit accidentally -- for a long time, and many of us are worried about our eroding infectious-disease surveillance-and-response capabilities," he says. "Internationally, funding is tenuous and in great need of improvement."
Still, sporadic attempts have been made to coordinate international efforts at controlling the disease. I witnessed one such effort, an international conference on malaria sponsored by the National Institutes of Health, the British Medical Research Council, and the French Institut Pasteur. It was a by-invitation-only affair held in a luxury resort hotel on the ocean about ten miles from Dakar. The President of Senegal, His Excellency Abdou Diouf, presided over the opening ceremonies, attended by a colorfully garbed entourage of ministers and ambassadors. President Diouf expressed his gratitude to the scientists for coming, and spoke gravely of malaria as one of the most terrible problems facing his nation, Africa, and indeed the world. Then he and his retinue left to a flutter of applause, and the session took on a Tower of Babel quality. Western scientists spoke of vaccine and drug development, of biotechnology, of manipulating and transplanting genes. African scientists spoke of a dearth of medical supplies and a lack of basic infrastructure, of bad roads and no refrigeration and a treatment population that thinks malaria comes from the sun. The one thing all parties seemed to agree on was that medical science has dismally failed to get a grip on the disease.
MALARIA is caused by infection with the Plasmodium genus of protozoan parasite. More than a hundred species of this parasite exist, capable of infecting reptiles, birds, rodents, and primates. Four species infect human beings, the most common being P. vivax and P. falciparum. The most pernicious is P. falciparum. It is not unheard of for an African child to go to school in the morning and die of falciparum infection in the afternoon. Understanding this adds perspective to the public obsession with other fast-acting microbes, such as so-called "flesh-eating" bacteria and the Ebola virus. The 1995 Ebola outbreak in Zaire that inspired Hollywood and transfixed the world caused approximately 250 deaths over a period of six months. More than twenty times that many Africans die every day of malaria.
Malaria parasites have spent centuries adapting to life in the human body, and as a result have grown cagey. Unlike human immunodeficiency virus, or HIV, which both infects and is transmitted by human beings, malaria parasites keep their delivery system separate from their food supply -- they do not shoot the messenger. The parasites are transmitted to human beings through the saliva of the female mosquito, which is so efficient at this task that it is sometimes described as a flying syringe. Once injected, the parasites quickly retreat to the liver, where they mature and multiply. It is not until they re-emerge in the bloodstream and invade the blood cells that symptoms appear. By this time the parasites have reproduced thousands of times. They thrash about, popping blood cells, clogging blood vessels, debilitating their host, and in some cases killing within hours.
Like HIV and tuberculosis, malaria does not elicit what is called a complete immune response in human beings: we can be infected with these microbes repeatedly, or carry them for any amount of time, without developing a full resistance to them. Nor do we develop a protective immune response to these diseases, as we do for such infections as polio, measles, and smallpox. Whatever immune reaction we develop appears to occur deep in the cell, and is devilishly difficult to elicit.
"HIV, TB, and malaria are among the most important infectious agents in the world," says Harold Varmus, the director of the National Institutes of Health. "There are no effective vaccines against them, and all have the same property of establishing chronic infection without an effective immune response." Malaria is perhaps the toughest of all, because, as a parasite, it has far more genetic material than a virus or a bacterium has. Never yet has a vaccine been proved successful against a parasite, and malaria is a particularly difficult target for a vaccine, because in each of the several stages it goes through, it has the opportunity to take hold in the host.